Radical cystectomy (RC) with bilateral pelvic lymphadenectomy with or without perioperative chemotherapy is the golden standard treatment in muscle invasive and recurrent high-grade non-muscle invasive urothelial carcinoma of the bladder (UCB). Despite treatment with curative intent, up to 50% of patients develop metastasis and die from UCB due to micro-metastatic disease undetectable for current staging techniques prior to definitive therapy. Tumor cell dissemination is a crucial step in the natural history of the metastatic cascade. Circulating tumor cells (CTC) are malignant epithelial cells detectable in the peripheral blood of patients with various malignancies. In UCB, CTC are detectable in a significant number of patients prior to RC and associated with inferior outcomes. In this review, we summarize the current literature regarding CTC in UCB, discussing their potential on clinical decision-making regarding multimodal treatment and implications on the application of novel targeted therapies in the future. There is reliable evidence that presence of CTC in clinically non-metastatic UCB patients treated with RC are a powerful predictor for unfavorable outcomes and may be useful for adjuvant chemotherapy decision-making and monitoring. However, currently, the evidence is limited, and thus, integration of CTC in future UCB clinical trials is strongly recommended to shed more light on the potential of this promising biomarker.
